ABSTRACT

Research question: This study aimed to establish the efficacy and safety of ovarian stimulation with a follitropin delta individualised fixed-dose regimen based on serum anti-Müllerian hormone (AMH) concentration and body weight versus conventional follitropin beta dosing in Japanese women.

Design: This randomised, controlled, assessor-blind, multicentre, non-inferiority trial was conducted in 347 Japanese in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) patients. They were randomised to individualised follitropin delta (AMH <15 pmol/l: 12 μg/day; AMH ≥15 pmol/l: 0.10–0.19 μg/kg/day; minimum 6 μg/day; maximum 12 μg/day) or conventional follitropin beta (150 IU/day for the first 5 days, with potential subsequent dose adjustments).

Primary endpoint: The primary endpoint was the number of oocytes retrieved with a pre-specified non-inferiority margin (−3.0 oocytes).

Secondary endpoints:

• Efficacy secondary endpoints included duration of stimulation, total gonadotrophin dose, distribution of number of oocytes retrieved, extreme ovarian response in at-risk populations (defined as <4 oocytes retrieved for women with AMH <15 pmol/l and ≥15 or ≥20 oocytes retrieved for women with AMH ≥15 pmol/l), pregnancy outcomes, including clinical pregnancy and live birth rates.
• Safety evaluations included adverse events, early and late ovarian hyperstimulation syndrome (OHSS), preventive interventions for early OHSS, cycle cancellation or blastocyst transfer cancellation due to excessive ovarian response/OHSS risk, and local tolerability.

Results: The primary trial objective was met, as non-inferiority was established for number of oocytes retrieved for individualised follitropin delta dosing compared with conventional follitropin beta dosing (9.3 versus 10.5; lower boundary of 95% CI−2.3). The occurrence of OHSS was reduced to approximately half with individualised compared with conventional dosing, with an incidence of 11.2% versus 19.8% (p=0.021) for OHSS of any grade and 7.1% versus 14.1% (p=0.027) for moderate/severe OHSS. The live-birth rate per started cycle was 23.5% for individualised dosing and 18.6% for conventional dosing.

Conclusions: Dosing with individualised follitropin delta in Japanese women is non-inferior to conventional dosing with follitropin beta for number of oocytes retrieved. The individualised approach shows a favourable benefit–risk profile, providing a statistically significant and clinically relevant reduction in the incidence of OHSS, without compromising live-birth rates.

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